This invention relates to novel processes for synthesizing intermediates in the preparation of N-aryl and N-heteroarylamide inhibitors of the enzyme acyl coenzyme A: cholesterol acyltransferase (ACAT), and to novel intermediates used in such processes.
The foregoing ACAT inhibitors having synthetic intermediates which may be prepared by the processes of this invention are described and claimed in PCT Patent Application PCT/US 89/04033, entitled "New N-Aryl and N-Heteroarylamide and Urea Derivatives as Inhibitors of Acyl Coenzyme A: Cholesterol Acyl Transferase" and filed Sep. 15, 1989. They are also described and claimed in the United States continuation-in-part application 648677 claiming priority from such PCT application and filed on Mar. 21, 1991. The present application claims priority as a continuation-in-part of United States parent application 648243 filed on Jan. 31, 1991. These ACAT inhibitors are useful in the prevention of atherosclerosis, myocardial infarction and stroke.
Cholesterol that is consumed in the diet (dietary cholesterol) is absorbed as free cholesterol by the mucosal cells of the small intestine. It is then esterified by the enzyme ACAT, packaged into particles known as chylomicrons, and released into the bloodstream. Chylomicrons are particles into which dietary cholesterol is packaged and transported in the bloodstream. By inhibiting the action of ACAT, the ACAT inhibitors referred to above prevent intestinal absorption of dietary cholesterol and thus lower serum cholesterol levels. They are therefore useful in preventing atherosclerosis, heart attacks and strokes.
Also, by inhibiting the action of ACAT, the ACAT inhibitors referred to above enable cholesterol to be removed from the walls of blood vessels. This activity renders such compounds useful in slowing or reversing the development of atherosclerosis as well as in preventing heart attacks and strokes.